Human skin is a structurally complex, relatively thick membrane comprised of two principal components, the outer epidermis and the underlying dermis, which is situated above the subcutaneous adipose or fat tissues.
The epidermis consists of four distinct layers, the stratum corneum, stratum granulosum, stratum spinosum, and stratum basale. In the skin of palms and soles only, there is normally one additional zone called the stratum lucidum between the stratum corneum and the stratum granulosum.
The dermis is comprised mainly of collagen, elastic fibers, glycosaminoglycans, and proteoglycans including hyaluronic acid, dermatan sulfate, and chondroitin sulfate, formerly known as mucopolysaccharides. Fibroblasts, the predominant cells of the dermis, synthesize collagen, elastic fibers, proteoglycans, and glycosaminoglycans. Collagen makes up approximately 77%, elastic fibers account for about 2%, and glycosaminoglycans constitute around 0.2% of the dry weight of the dermis. Collagen provides the tensile strength of and elastic fibers give resilience to the dermis. The glycosaminoglycans bind water to form a gelatinous mass between collagen and elastic fibers, which acts as a lubricant and shock absorber for the dermis during movement of the skin.
Cutaneous aging, while having epidermal concomitants, primarily involves dermal and subcutaneous changes, and is caused by (a) internal factors alone, as in intrinsic aging and (b) external factors, as in extrinsic aging. Intrinsic aging is also known as natural or chronologic aging, and extrinsic aging is often called photoaging. “Photodamage” implies skin damage caused by chronic sun exposure. These terms may be described as follows.
Intrinsic aging of skin, in sun-protected skin of the upper arm and abdomen, is an inherent degenerative process due to declining physiologic functions and capacities. Such aging process may include qualitative and quantitative skin changes and includes diminished or defective synthesis of collagen and elastic fibers, and proteoglycans and glycosaminoglycans in the dermis. Signs of intrinsic aging include progressive thinning of skin, deepening of skin lines and fine wrinkles, lusterless skin surface, and loss of skin elasticity and recoilability. Although intrinsic aging of living creatures is neither reversible nor preventable, modification and improvement of skin signs associated with such aging process can be achieved through topical management.
Extrinsic aging of skin is a distinctive process caused by external factors, which include sunlight, radiation, air pollution, wind, cold, dampness, heat, and chemicals.
Photoaging of skin may be defined as destructive cutaneous changes caused by chronic exposure to sunlight. Signs of photoaging on the face and back of hands include coarse and deepened wrinkles due to changes and degeneration of collagen and elastic fibers; marked loss of elasticity and recoilability; leathery skin surface and skin lesions with abnormal pigmentation and increased numbers of age spots, pigmented spots, blotches and nodules. Histologically, the qualities and quantities of elastin and collagen tissues are changed. Normal elastin in tissues is replaced by abnormal elastin characterized as solar elastosis, and the normal collagen fibers are decreased.
Photodamage of skin, also called solar damage, may be defined as cutaneous damage caused by chronic exposure to solar radiation and is associated with development of neoplastic lesions. Skin disorders caused by photodamage include pre-malignant lesions, basal cell carcinomas, squamous cell carcinomas, and malignant melanomas.
The intact skin of humans is an effective barrier to many natural and synthetic substances. Many cosmetic and pharmaceutical agents, which are pharmacologically effective on oral or systemic administration, may be much less effective or even totally ineffective, when applied topically to the skin. Therefore, there is an ongoing need in the art for new and effective regimens for treating aging-related skin conditions. The present invention addresses these and other needs in the art by providing novel methods and topical formulations for treating a variety of aging-related skin conditions, including wrinkles, age spots, sun damage (particularly UV radiation-induced oxidative stress), blemishes, hyperpigmented skin, age spots, increased skin thickness, loss of skin elasticity and collagen content, dry skin, lentigines, and melasmas. Treatment is effected by topical application of a cosmeceutically active base, a surprisingly effective yet simple means for treating aging-related skin conditions. To the best of applicants' knowledge, the use of cosmeceutically active bases as disclosed herein has not been suggested in the art and represents a significant and unexpected advance in the art.